S173: RETROSPECTIVE STUDY OF LENALIDOMIDE DISCONTINUATION IN PATIENTS WITH MYELODYSPLASTIC SYNDROME HARBORING DEL(5Q). A HARMONY ALLIANCE STUDY
Authors: Elena Crisà, María Díez Campelo, Ulrich Germing, Elvira Mora Castera, Francisca Hernandez Mohedo, Kündgen Andrea, Ebeling Freja, Mikko Myllymäki, Martin Jädersten, Eva Hellström Lindberg, Detlef Haase, Isabella Capodanno, Antonella Poloni, Carlo Finelli, Monica Crugnola, Claudio Fozza, Anna Calvisi, Chiara Frairia, Giuseppe Pietrantuono, Marco Cerrano, Rosanna Ciancia, Daniela Barraco, Wolf-Karsten Hofmann, Axel Ruefer, Cécile Bally, Pierre Fenaux, Guillermo Sanz Santillana, Valeria Santini
Journal: HemaSphere (2023)

Background: Lenalidomide can lead to red blood cell-transfusion independence (RBC-TI) in 60-70% of del(5q) transfusion dependent MDS patients, and to complete cytogenetic response (CCyR) in 30-40% of them. Currently, patients achieving RBC-TI and CCyR are suggested to continue treatment indefinitely. However, the optimal duration of lenalidomide therapy has never been formally addressed. Besides, lenalidomide is associated with possibly serious side effects and high treatment costs and could potentially trigger disease progression. Some small retrospective experiences showed that the majority of RBC-TI patients who stopped lenalidomide maintained the response. Aims: This study aimed to investigate the outcome of patients with del(5q) MDS RBC-TI who discontinue lenalidomide in RBC-TI response. The primary end point was event free survival (EFS) (events included RBC-TI loss, CCyR loss, disease progression, lenalidomide re-start or death). Secondary end points were RBC-TI duration, overall survival (OS), progression free survival. Methods: Within the MDS working group of the Harmony project, we retrospectively included patients from different European Countries (Italy, Germany, Spain, France, Finland, Switzerland, Sweden) with a del(5q) MDS diagnosis according to 2008 or 2016 WHO classification, at IPSS-r very low, low or intermediate at lenalidomide treatment start, who discontinued therapy after achieving RBC-TI. Patients who stopped lenalidomide for lack of response or disease progression were excluded. Results: We included 114 del(5q) MDS patients who started lenalidomide between December 2003 and January 2021 and discontinued treatment between July 2004 and March 2022. Median age was 77 years (range 42-93) and 81.6% were female. After a median of 12 lenalidomide cycles (range 1-70) before discontinuation, all the patients achieved RBC-TI, 12% also a partial CyR and 41% a CCyR. The reason for lenalidomide stop was intolerance for 71 patients (62%), optimal response for 32 (28%), patient decision for 9 (8%) and clonal evolution for 2 (2%).After a median follow-up of 44 months 40% of patients (n 46) lost RBC-TI, 55% lost CCyR (25 out of 45 who had a cytogenetic re-evaluation), 24% (n 27) progressed to high risk MDS or acute myeloid leukemia and 38% (n 44) died. Median EFS was 36 months (range 1-129) and was affected by IPSSr (p=0.035) and by treatment duration (> o ≤ 12 cycles) before discontinuation (median 53 vs 26 months, p=0.007). Median duration of RBC-TI was 60 months (range 1-119) and was longer for patients who achieved a CCyR before discontinuation (median 85 vs 35 months, p=0.028 Fig A) and received more than 12 lenalidomide cycles (median 86 vs 35 months, p <0.001 Fig B). However, patients who lost RBC-TI had a shorter survival (median 71 vs 101 months, p=0.046). Forty-six patients were re-treated with lenalidomide for response loss and 56% of them achieved at least a hematological response (3 also a CCyR). Summary/Conclusion: This is the largest series to date exploring the outcome of MDS del(5q) patients who discontinue lenalidomide while in RBC-TI response. Lacking prospective studies on the optimal duration of lenalidomide treatment, our retrospective data suggest that stopping lenalidomide in responding patients, particularly after at least 12 months of treatment and achievement of CCyR, is possible and may spare toxicities, reduce the economic impact on national healthcare systems and likely improve patients' quality of life. Prospective studies could confirm this promising data.Keywords: Therapy, Health care, MDS